Drug information of Mirabegron

Mechanism of effect

Mirabegron is a potent and selective agonist for beta-3 adrenergic receptors. Once beta-3 receptors are activated, the detrusor smooth muscle relaxes to allow for a larger bladder capacity. At higher doses (200 mg), there is a potential for mirabegron to activate beta-1 and beta-2 adrenergic receptors.

Pharmacodynamic

Mirabegron increases blood pressure in a dose dependent manner. However, this effect is reversible when mirabegron is discontinued. Mirabegron also increases heart rate in a dose dependent manner.

Pharmacokinetics

Bioavailability: 29% (25-mg), 35% (50-mg)

Peak Plasma Time: 3.5 hr

Peak Plasma Concentration: ~3-fold increase from 50 mg dose to 100 mg dose

AUC: ~2.5-fold increase from 50 mg dose to 100 mg dose

Steady state: 7 days

Protein Bound: 71%

Vd, steady state: 1670 L

Metabolism

Via multiple pathways including dealkylation, (direct) glucuronidation, amide hydrolysis, and minimal oxidative metabolism in vivo by CYP2D6 and CYP3A4

Possible involvement of butylcholinesterase, uridinediphospho-glucuronosyltransferases (UGT) and alcohol dehydrogenase

Moderate CYP2D6 inhibitor

Half-Life: 50 hr

Total body clearance: 57 L/hr (following IV administration)

Excretion: Urine (55%); feces (34%)

Excretion, unchanged: Urine (~25%); feces (0%)

Drug indications

Dosage

Adult

Overactive Bladder

• 25 mg PO qDay
• 25 mg dose is typically effective within 8 weeks
• May increase to 50 mg PO qDay based on individual efficacy and tolerability

Pediatric

Safety and efficacy not established

Drug contraindications

Side effects

Interactions

Alerts

May increase blood pressure; monitor blood pressure periodically, especially in hypertensive patients; not recommended for use in severe uncontrolled hypertensive patients (defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg)

Urinary retention may occur with bladder outlet obstruction or with concomitant antimuscarinic therapy; administer with caution in these patients

Angioedema of the face, lips, tongue, and/or larynx reported; may occur after the first dose or following multiple doses; promptly discontinue and initiate appropriate therapy to ensure a patent airway

Drug interactions overview

• Appropriate monitoring is recommended and dose adjustment may be necessary for narrow therapeutic index CYP2D6 substrates
• Coadministration of digoxin 0.25 mg with a combination of solifenacin 5 mg and mirabegron 50 mg increased digoxin AUC and peak plasma concentration by ~10% and 14%, respectively; for patients who are initiating a combination of mirabegron and digoxin, consider initiating lowest dose for digoxin; monitor serum digoxin concentrations and titrate digoxin dose to obtain the desired clinical effect
• In studies, ketoconazole increased mirabegron peak plasma concentration by 45% and mirabegron AUC by 80% after multiple dose administration of 400 mg of ketoconazole for 9 days prior to the administration of a single dose of 100 mg mirabegron in 23 male and female healthy subjects

Points of recommendation

• It may take several weeks to see the full effects.
• High blood pressure has happened with mirabegron. Have your blood pressure checked as you have been told by your doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using mirabegron while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

• Take with or without food.
• Swallow whole. Do not chew, break, or crush.
• Take with a full glass of water.

• Skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Pregnancy level

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